The function of glutaredoxin GRXS15 is required for lipoyl-dependent dehydrogenases in mitochondria
Moseler, Anna and Kruse, Inga and Maclean, Andrew E and Pedroletti, Luca and Franceschetti, Marina and Wagner, Stephan and Wehler, Regina and Fischer-Schrader, Katrin and Poschet, Gernot and Wirtz, Markus and Dörmann, Peter and Hildebrandt, Tatjana M and Hell, Rüdiger and Schwarzländer, Markus and Balk, Janneke and Meyer, Andreas J (2021) The function of glutaredoxin GRXS15 is required for lipoyl-dependent dehydrogenases in mitochondria. Plant Physiology, 186 (3). pp. 1507-1525. ISSN 1532-2548 (https://doi.org/10.1093/plphys/kiab172)
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Abstract
Iron–sulfur (Fe–S) clusters are ubiquitous cofactors in all life and are used in a wide array of diverse biological processes, including electron transfer chains and several metabolic pathways. Biosynthesis machineries for Fe–S clusters exist in plastids, the cytosol, and mitochondria. A single monothiol glutaredoxin (GRX) is involved in Fe–S cluster assembly in mitochondria of yeast and mammals. In plants, the role of the mitochondrial homolog GRXS15 has only partially been characterized. Arabidopsis (Arabidopsis thaliana) grxs15 null mutants are not viable, but mutants complemented with the variant GRXS15 K83A develop with a dwarf phenotype similar to the knockdown line GRXS15 amiR. In an in-depth metabolic analysis of the variant and knockdown GRXS15 lines, we show that most Fe–S cluster-dependent processes are not affected, including biotin biosynthesis, molybdenum cofactor biosynthesis, the electron transport chain, and aconitase in the tricarboxylic acid (TCA) cycle. Instead, we observed an increase in most TCA cycle intermediates and amino acids, especially pyruvate, glycine, and branched-chain amino acids (BCAAs). Additionally, we found an accumulation of branched-chain a-keto acids (BCKAs), the first degradation products resulting from transamination of BCAAs. In wild-type plants, pyruvate, glycine, and BCKAs are all metabolized through decarboxylation by mitochondrial lipoyl cofactor (LC)-dependent dehydrogenase complexes. These enzyme complexes are very abundant, comprising a major sink for LC. Because biosynthesis of LC depends on continuous Fe–S cluster supply to lipoyl synthase, this could explain why LC-dependent processes are most sensitive to restricted Fe–S supply in grxs15 mutants.
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Item type: Article ID code: 77679 Dates: DateEvent15 April 2021Published15 April 2021AcceptedSubjects: Agriculture > Plant culture
Science > Botany
Science > PhysiologyDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Professional Services > Information Services
Strathclyde Business School > Management ScienceDepositing user: Pure Administrator Date deposited: 07 Sep 2021 12:55 Last modified: 20 Oct 2024 00:43 URI: https://strathprints.strath.ac.uk/id/eprint/77679